Intrahepatic cholangiocarcinoma
Intrahepatic cholangiocarcinoma starts in the small bile ducts inside the liver and usually appears as a liver mass rather than causing jaundice. It is the biliary cancer with the most drug targets: FGFR2 fusions treated with pemigatinib or futibatinib, IDH1 mutations with ivosidenib, and for everyone chemotherapy with the immunotherapy durvalumab or pembrolizumab.
Overview
Intrahepatic cholangiocarcinoma arises from the bile ducts beyond the second-order branches within the liver and presents as a mass, often found incidentally or with vague pain and weight loss, in contrast to the jaundice of extrahepatic tumours. Risk factors include cirrhosis, hepatitis B and C, primary sclerosing cholangitis, liver flukes in Thailand and neighbouring countries, and hepatolithiasis, but most cases in the West have none. Its genome differs from that of the rest of the biliary tree: FGFR2 fusions occur in about 10 to 15 percent, IDH1 mutations in about 15 percent, and BAP1 and ARID1A mutations are common, whereas KRAS and HER2 alterations are less frequent than in extrahepatic disease, so comprehensive sequencing at diagnosis is standard.
Resection is the only cure and is possible in a minority; hepatectomy with lymph node dissection is followed by six months of capecitabine after the BILCAP trial, whose per-protocol analysis showed longer survival. Recurrence is common. Liver transplantation for very early tumours in cirrhotic livers and after chemotherapy for locally advanced disease is under study, and for unresectable liver-confined disease radioembolisation, stereotactic radiotherapy and hepatic artery infusion chemotherapy are used in specialised centres.
For advanced disease gemcitabine with cisplatin (ABC-02, 2010) was the standard for a decade until TOPAZ-1 (2022) added durvalumab and KEYNOTE-966 (2023) added pembrolizumab, each modestly improving survival and producing a tail of long-term responders. After chemotherapy, targeted drugs matched to the tumour's mutation are given: pemigatinib (FIGHT-202, response rate 36 percent) and futibatinib (FOENIX-CCA2, response rate 42 percent) for FGFR2 fusions, and ivosidenib for IDH1 mutations, which in ClarIDHy extended progression-free survival from 1.4 to 2.7 months and gave a survival benefit once crossover was accounted for. Acquired resistance to FGFR inhibitors through gatekeeper mutations is tracked with circulating tumour DNA, and next-generation FGFR2 inhibitors such as tinengotinib are in trials.
State of the art
- Intrahepatic cholangiocarcinoma was the first gastrointestinal cancer with an approved FGFR inhibitor and the first solid tumour with an approved IDH1 inhibitor.
- Immunotherapy added to gemcitabine-cisplatin is now first-line standard across biliary cancers.
- Tracking resistance with circulating tumour DNA and switching FGFR inhibitors is becoming routine in specialist centres.
Red cards
From the labels and guidelines behind the standard of care. Your team's thresholds win.- Emergency services nowBleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
- Emergency services nowFainting or palpitations
Fainting, near-fainting, or an irregular or racing heartbeat; several kinase inhibitors prolong the QT interval and the labels require ECG and electrolyte monitoring.
- Emergency services nowHypophysitis or adrenal crisis
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
- Emergency services nowBlood clot (lenalidomide, pomalidomide, thalidomide)
A swollen painful calf, or sudden breathlessness with chest pain; venous and arterial thromboembolism is a boxed warning and blood-thinning prophylaxis is recommended.
- Emergency services nowDifferentiation syndrome
Fever, cough or breathlessness, rapid weight gain or swelling, bone pain, low blood pressure or reduced urine; the labels say to start steroids and monitor at the first suspicion, and the syndrome has been fatal.
- Check before combiningFood and drink: Pembrolizumab
No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
See all on the product pages:CapecitabineDurvalumabFOLFOX (5-FU, leucovorin, oxaliplatin)FutibatinibGemcitabine + cisplatinIvosidenibPembrolizumabPemigatinib·Printable cards in the navigator
Anatomy and lymph node drainage
- Pancreatic head (most PDAC)
- Body and tail
- Ampulla
- Islets (pancreatic NET)
- Intrahepatic ducts
- Perihilar (Klatskin)
- Distal bile duct
- Gallbladder
- Nodes: peripancreatic
- Nodes: hepatic hilar
- Nodes: coeliac and superior mesenteric
Most pancreatic cancers arise in the head next to the bile duct, which is why jaundice is the presenting sign; bile duct cancers are named by where along the tree they sit.
- Pancreatic head (most PDAC)
- Body and tail
- Ampulla
- Islets (pancreatic NET)
- Intrahepatic ductsMass-forming intrahepatic cholangiocarcinoma (most) · Intrahepatic cholangiocarcinoma with FGFR2 fusion (pemigatinib, futibatinib) · Intrahepatic cholangiocarcinoma with IDH1 mutation (ivosidenib) · Fluke-associated intrahepatic cholangiocarcinoma
- Perihilar (Klatskin)
- Distal bile duct
- Gallbladder
- peripancreatic
- hepatic hilar
- coeliac and superior mesenteric
Same organ: Pancreatic ductal adenocarcinoma, Biliary tract cancer (cholangiocarcinoma), Extrahepatic cholangiocarcinoma (perihilar and distal), Biliary tract cancer (all types), Neuroendocrine tumours, Gallbladder cancer, Ampullary cancer (ampulla of Vater)
Bile duct cancer arising within the liver, the second commonest primary liver cancer after hepatocellular carcinoma and rising in incidence worldwide; it carries most of the targetable mutations in biliary cancer, with FGFR2 fusions in about one in eight and IDH1 mutations in about one in seven.
- Liquid biopsy (ctDNA)Standard of care
- MRIStandard of care
Nothing recorded yet.
Nothing recorded yet.
Also on OnCo: Symptoms and red flags · Early detection roadmap.
Cases by country
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Contrast MRI and CT, biopsy, and comprehensive genomic profiling including RNA-based fusion detection for every patient.
Hepatectomy with lymph node dissection followed by six months of adjuvant capecitabine (BILCAP).
Radioembolisation, stereotactic radiotherapy or hepatic artery infusion in specialised centres, usually with systemic therapy; liver transplantation in trials.
Gemcitabine and cisplatin with durvalumab (TOPAZ-1) or pembrolizumab (KEYNOTE-966).
Pemigatinib (FIGHT-202) or futibatinib (FOENIX-CCA2); management of hyperphosphataemia and eye toxicity.
FOLFOX (ABC-06); trials.
Subtypes & biomarkers
top- Mass-forming intrahepatic cholangiocarcinoma (most)
- Intrahepatic cholangiocarcinoma with FGFR2 fusion (pemigatinib, futibatinib)
- Intrahepatic cholangiocarcinoma with IDH1 mutation (ivosidenib)
- Small-duct versus large-duct type
- Fluke-associated intrahepatic cholangiocarcinoma
- Combined hepatocellular-cholangiocarcinoma
- FGFR2 fusions and rearrangements (RNA or DNA sequencing)
- IDH1 mutation
- BAP1, ARID1A and PBRM1 (small-duct type)
- HER2, BRAF V600E, NRG1 and microsatellite instability (less common)
- CA 19-9 for monitoring
- Circulating tumour DNA for resistance mutations under FGFR inhibition
How often this target appears
- 2010ABC-02: gemcitabine plus cisplatin becomes the standard for advanced biliary cancer
- 2019BILCAP: adjuvant capecitabine after resection
- 2020FIGHT-202: pemigatinib approved for FGFR2 fusion-positive cholangiocarcinoma
- 2021ClarIDHy: ivosidenib approved for IDH1-mutant cholangiocarcinoma
- 2022FOENIX-CCA2: futibatinib approved; TOPAZ-1: durvalumab added to chemotherapy
- 2023KEYNOTE-966: pembrolizumab added to chemotherapy
Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.
All 15 changes by month →- 2026-09-17This recordIntrahepatic cholangiocarcinomaFacts on this page last checked
When this page itself was last checked or edited.
- 2023Trial resultKEYNOTE-966KEYNOTE-966 reported
OS 12.
- 2023MilestoneKEYNOTE-966KEYNOTE-966: pembrolizumab added to chemotherapy
A milestone in how this cancer is treated.
- 2022ApprovalFutibatinibFutibatinib approved in US
Previously treated FGFR2-fusion/rearranged intrahepatic cholangiocarcinoma (accelerated)
- 2022Trial resultFOENIX-CCA2FOENIX-CCA2 reported
ORR 42%; PFS 9.
- 2022Trial resultTOPAZ-1TOPAZ-1 reported
OS HR 0.
What is in development for Intrahepatic cholangiocarcinoma, drawn from the whole corpus: 10 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.
Drugs in phase 3 · 1
Trials under way · 1
- FIRST-308 · phase 3 · TransThera
Trials reported · 6
- BILCAP · phase 3 · 2017 · mixed
- ClarIDHy · phase 3 · 2020 · positive
- FIGHT-202 · phase 2 · 2020 · positive
- FOENIX-CCA2 · phase 1/2 · 2022 · positive
- KEYNOTE-966 · phase 3 · 2023 · positive
- TOPAZ-1 · phase 3 · 2022 · positive
Combinations being explored · 1
Ideas not yet in a trial · 1
Open problems and what is being done
Most patients present unresectable, and recurrence after resection is common.
and how the field plans to fix it →What is being done about thisRecurrence and residual diseaseAvailable now- Liquid biopsy (ctDNA)Standard of care
In trialsNothing recorded yet.
Ideas and roadmapsNothing recorded yet.
Also on OnCo: Treatment journeys · Survivorship planner.
FGFR inhibitor resistance develops within a year through kinase domain mutations.
and how the field plans to fix it →What is being done about thisResistance to treatmentAvailable now- Comprehensive genomic profilingStandard of care
- Liquid biopsy (ctDNA)Standard of care
In trials- TinengotinibPhase 3
Ideas and roadmapsAlso on OnCo: Resistance atlas · Lines of therapy.
Rising incidence in Western countries without a clear cause.
Trials
topTrials recruiting now
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Landmark trials
Expert centres
topExpert centres
New York · cancer center | United States | 0 | 5,100 | 94,456 | #1 | ||
Seoul · hospital | South Korea | none recorded | 0 | 1,177 | 18,820 | none recorded | #4 |
Rochester, MN · hospital | United States | 0 | 4,511 | 44,748 | #5 | ||
Baltimore · cancer center | United States | 0 | 2,955 | 41,449 | #10 | ||
Stanford · university | United States | 0 | 3,000 | 50,162 | #30 | ||
London · consortium | United Kingdom | none recorded | 2 | not matched | - | none recorded | - |
Shanghai · hospital | China | none recorded | 0 | 2,872 | 31,534 | - | |
London · hospital | United Kingdom | none recorded | 0 | 2,376 | 28,940 | - | |
Dallas, TX · cancer center | United States | 0 | 1,744 | 19,757 | - | ||
Utrecht · cancer center | Netherlands | none recorded | 0 | 1,422 | 20,323 | - | |
Lyon · cancer center | France | none recorded | 0 | 1,071 | 14,301 | - | |
Rozzano (Milan) · hospital | Italy | none recorded | 0 | 1,031 | 10,720 | - | |
Naples · cancer center | Italy | none recorded | 0 | 961 | 15,028 | - | |
Oslo · cancer center | Norway | none recorded | 0 | 936 | 11,600 | - | |
Jinan · cancer center | China | none recorded | 0 | 920 | 7,804 | - |
These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with Intrahepatic cholangiocarcinoma but is thinly recorded here will look small.
Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.
Questions to ask
topQuestions to ask your oncologist about Intrahepatic cholangiocarcinoma
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example FGFR2 fusions and rearrangements, IDH1 mutation, BAP1, ARID1A and PBRM1, HER2, BRAF V600E, NRG1 and microsatellite instability, CA 19-9 for monitoring), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include Mass-forming intrahepatic cholangiocarcinoma, Intrahepatic cholangiocarcinoma with FGFR2 fusion, Intrahepatic cholangiocarcinoma with IDH1 mutation.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Diagnosis
- For my situation (diagnosis), which of the standard options do you recommend and why?Why: Guideline options include: Contrast MRI and CT, biopsy, and comprehensive genomic profiling including RNA-based fusion detection for every patient.
Resectable
- For my situation (resectable), which of the standard options do you recommend and why?Why: Guideline options include: Hepatectomy with lymph node dissection followed by six months of adjuvant capecitabine (BILCAP).
- Am I a candidate for Capecitabine, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of BILCAP apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Unresectable, liver-confined
- For my situation (unresectable, liver-confined), which of the standard options do you recommend and why?Why: Guideline options include: Radioembolisation, stereotactic radiotherapy or hepatic artery infusion in specialised centres, usually with systemic therapy; liver transplantation in trials.
Advanced, first line
- For my situation (advanced, first line), which of the standard options do you recommend and why?Why: Guideline options include: Gemcitabine and cisplatin with durvalumab (TOPAZ-1) or pembrolizumab (KEYNOTE-966).
- Am I a candidate for Gemcitabine + cisplatin, Durvalumab, Pembrolizumab, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of TOPAZ-1 and KEYNOTE-966 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Advanced, FGFR2 fusion after chemotherapy
- For my situation (advanced, fgfr2 fusion after chemotherapy), which of the standard options do you recommend and why?Why: Guideline options include: Pemigatinib (FIGHT-202) or futibatinib (FOENIX-CCA2); management of hyperphosphataemia and eye toxicity.
- Am I a candidate for Pemigatinib, Futibatinib, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of FIGHT-202 and FOENIX-CCA2 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Advanced, IDH1 mutation after chemotherapy
- For my situation (advanced, idh1 mutation after chemotherapy), which of the standard options do you recommend and why?Why: Guideline options include: Ivosidenib (ClarIDHy).
- Am I a candidate for Ivosidenib, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of ClarIDHy apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Second line without a target
- For my situation (second line without a target), which of the standard options do you recommend and why?Why: Guideline options include: FOLFOX (ABC-06); trials.
- Am I a candidate for FOLFOX (5-FU, leucovorin, oxaliplatin), and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Any stage
- Are there clinical trials I could join, for example of Tinengotinib, FIRST-308, ctDNA-guided switching among FGFR inhibitors, Liquid biopsy (ctDNA)?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “Most patients present unresectable, and recurrence after resection is common”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “FGFR inhibitor resistance develops within a year through kinase domain mutations”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
Newly diagnosed? Read the first 60 days with Intrahepatic cholangiocarcinoma, then print the one-page appointment sheet with room for the answers.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
14targets
5drugs
10companies
10terms
4trials
8pairings
1ideas
1Latest papers
topQuery for this cancer: (TITLE:"Intrahepatic cholangiocarcinoma" OR ABSTRACT:"Intrahepatic cholangiocarcinoma" OR TITLE:"iCCA" OR ABSTRACT:"iCCA" OR TITLE:"Intrahepatic bile duct cancer" OR ABSTRACT:"Intrahepatic bile duct cancer" OR TITLE:"Peripheral cholangiocarcinoma" OR ABSTRACT:"Peripheral cholangiocarcinoma" OR TITLE:"Mass-forming cholangiocarcinoma" OR ABSTRACT:"Mass-forming cholangiocarcinoma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Intrahepatic cholangiocarcinoma, not a curated reading list.
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